ABSTRACT
In the central nervous system, nitric oxide (NO) is associated with many pathological diseases such as brain ischemia, neurodegeneration and inflammation. The epigallocatechin gallate (EGCG), a major compound of green tea, is recognized as protective substance against neuronal diseases. This study is aimed to investigate the effect of EGCG on NO-induced cell death in PC12 cells. Administration of sodium nitroprusside (SNP), a NO donor, decreased cell viability in a dose- and time-dependent manner and induced genomic DNA fragmentation with cell shrinkage and chromatin condensation. EGCG diminished the decrement of cell viability and the formation of apoptotic morphologenic changes as well as DNA fragmentation by SNP. EGCG played as an antioxidant that attenuated the production of reactive oxygen species (ROS) by SNP. The cells treated with SNP showed downregulation of Bcl-2, but upregulation of Bax. EGCG ameliorated the altered expression of Bcl-2 and Bax by SNP. The release of cytochrome c from mitochondria into cytosol and expression of voltage -dependent anion channel (VDAC) 1, a cytochrome c releasing channel in mitochondria, were increased in SNP-treated cells, whereas were attenuated by EGCG. The enhancement of caspase-9, preceding mitochondria-dependent pathway, caspase-8 and death receptor-dependent pathway, as well as caspase-3 activities were suppressed by EGCG. SNP upragulated Fas and Fas-L, which are death receptor assembly, whereas EGCG ameliorated the expression of Fas enhanced by SNP. These results demonstrated that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells, through scavenging ROS and regulating the mitocondria- and death receptor-mediated signal pathway. The present study suggest that EGCG might be a natural neuroprotective substance.
Subject(s)
Animals , Humans , Apoptosis , Brain Ischemia , Caspase 3 , Caspase 8 , Caspase 9 , Cell Death , Cell Survival , Central Nervous System , Chromatin , Cytochromes c , Cytosol , DNA Fragmentation , Down-Regulation , Inflammation , Mitochondria , Neurons , Nitric Oxide , Nitroprusside , PC12 Cells , Reactive Oxygen Species , Signal Transduction , Tea , Tissue Donors , Up-RegulationABSTRACT
The salivary glands produce 1.5 l of fluid per day. As in other organs, the general paradigm in the salivary glands is that water movement occurs secondary to osmotic driving forces created by active salt transport. Therefore, high water permeability in salivary glands is expected to need a variety of aquaporin (AQP), a water channel. Although four AQPs have been known to reside in salivary glands, the precise location and roles of AQPs have been not well examined. This study is aimed to investigate the distribution of AQPs in 3 major salivary glands and their changes after cholinergic stimulation using immunohistochemical study in Sprague Dawley rats weighing 300 g under pentobarbital sodium anesthesia. AQP1 was localized in the endothelial cells of all salivary capillary vessels and the myoepithelial cells. AQP4 was demonstrated in the epithelium of the excretory ductal cells of all salivary glands. AQP5 and 8 were abundantly present in the basolateral membrane and apical membranes of the serous acini including intercellular secretory canaliculi, whereas AQP5 was weakly present in mucous acini. In addition, AQP5 was found in the epithelium of the intercalated and striated ducts. Upon stimulation of carbachol (10 micro gram/kg, I.P). AQP5 and 8 tended to translocate from basolateral membrane to the apical membrane, appearing as clusters of dots. These results suggest that AQP5 and 8 are the candidate molecules responsible for the water movement in salivary acinar cells.